Downregulation of hsa_circ_0004543 Activates oxLDL-Induced Vascular Endothelial Cell Proliferation and Angiogenesis

Han, Lu; Li, Dandan; Hang, Yanwen; Xiaojuan, Zong; Lv, Jiashun; Bai, Xiaolu; Lü, Yi; Zhang, Peng; Zhou, Meiling; Wu, Zhengli; Hu, Wei

doi:10.3389/fgene.2021.632164

Cited by 11 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…apoptosis of oxLDL-stimulated endothelial cells [210][211][212], macrophages [213,214], and VSMCs [215,216].…”

Section: Discussionmentioning

confidence: 99%

“…CircRNAs are stable and rich in miR-binding sites that serve as miR sponges or competitive endogenous RNAs. Currently, it has been shown that they are able to modulate the proliferation, migration, inflammatory response, and apoptosis of oxLDL-stimulated endothelial cells [ 210 , 211 , 212 ], macrophages [ 213 , 214 ], and VSMCs [ 215 , 216 ].…”

Section: The Oxldl Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Oxidized LDLs as Signaling Molecules

2021

View full text Add to dashboard Cite

Levels of oxidized low-density lipoproteins (oxLDLs) are usually low in vivo but can increase whenever the balance between formation and scavenging of free radicals is impaired. Under normal conditions, uptake and degradation represent the physiological cellular response to oxLDL exposure. The uptake of oxLDLs is mediated by cell surface scavenger receptors that may also act as signaling molecules. Under conditions of atherosclerosis, monocytes/macrophages and vascular smooth muscle cells highly exposed to oxLDLs tend to convert to foam cells due to the intracellular accumulation of lipids. Moreover, the atherogenic process is accelerated by the increased expression of the scavenger receptors CD36, SR-BI, LOX-1, and SRA in response to high levels of oxLDL and oxidized lipids. In some respects, the effects of oxLDLs, involving cell proliferation, inflammation, apoptosis, adhesion, migration, senescence, and gene expression, can be seen as an adaptive response to the rise of free radicals in the vascular system. Unlike highly reactive radicals, circulating oxLDLs may signal to cells at more distant sites and possibly trigger a systemic antioxidant defense, thus elevating the role of oxLDLs to that of signaling molecules with physiological relevance.

show abstract

“…apoptosis of oxLDL-stimulated endothelial cells [210][211][212], macrophages [213,214], and VSMCs [215,216].…”

Section: Discussionmentioning

confidence: 99%

Section: The Oxldl Signalingmentioning

confidence: 99%

Oxidized LDLs as Signaling Molecules

2021

View full text Add to dashboard Cite

show abstract

“…Reportedly, circRNAs feature prominently in multiple cardiovascular diseases [ 7 ]. For example, circ_0004543 is highly expressed in ox-LDL-initiated human umbilical vein endothelial cells (HUVECs), and circ_0004543 depletion increases the growth of ox-LDL-caused HUVECs [ 8 ]. circ_0065149 restrains ox-LDL-caused apoptosis and inflammation of HUVECs via targeting miR-330-5p [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ_0026218 Suppressed Atherosclerosis Progression via miR‐338‐3p/SIRT6 Axis

Yang¹,

Chen²,

Li³

et al. 2023

BioMed Research International

View full text Add to dashboard Cite

Background. Multiple circular RNAs (circRNAs) are implicated in atherosclerosis (AS) pathogenesis. In fact, how circRNA 0026218 (circ_0026218) functions in AS remains unknown, and thus the functions and mechanisms of circ_0026218 in the injury of vascular endothelial cells are to be investigated. Methods. Microarray analysis was employed to screen out differentially expressed circRNAs in AS. A cell model was mimicked by treating Human umbilical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL). circ_0026218, microRNA-338-3p (miR-338-3p) and silent information regulator 6 (SIRT6) expressions in HUVECs with ox-LDL treatment were probed by qRT-PCR. The cell proliferative capabilities were exposed by CCK-8 assay. The contents of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α) were measured by ELISA. Oxidative stress kits were utilized to detect the levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA). Flow cytometry was adopted to analyze the level of apoptosis of HUVECs. Dual-luciferase reporter gene assay and RIP assay were leveraged to expose the interplay between miR-338-3p and circ_0026218 or SIRT6 3 ′ -UTR, respectively. In addition, the impacts of circ_0026216 and miR-338-3p on SIRT6 protein expressions were subjected to Western blot. Results. circ_0026218 was greatly depleted in ox-LDL-stimulated HUVECs. circ_0026218 overexpression promoted viability of HUVECs in vitro and inhibited inflammatory response, oxidative stress, and apoptosis. circ_0026218 could adsorb miR-338-3p and positively modulated SIRT6 expressions via sponging miR-338-3p. Upregulation of this miRNA reversed the influence of circ_0026218 overexpression on ox-LDL-caused injury and apoptosis of HUVECs. Conclusion. Collectively, circ_0026218 upregulates SIRT6 expression through decoying miR-338-3p, thereby inhibiting ox-LDL-initiated injury of HUVECs. circ_0026218 is involved in the pathogenesis of AS.

show abstract

“…And oxLDL can enhance the tumor-induced angiogenesis to promote the vascular metastasis of cancer cells (Han et al, 2021), indicating that oxLDL may promote the EMS-induced angiogenesis assisting the EMS vascular metastasis. Tumor-angiogenesis needs vascular epithelial factors like VEGF-A, VEGF-B and PDGF, to initiate the proliferation and migration of vascular epithelial cells(Claesson-Welsh and Welsh, 2013, Saharinen et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

oxLDL promotes EMS-induced angiogenesis by up-regulating VEGF-A expression and secretion of endometrial cells

Huang

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Endometriosis (EMS) is a "tumor-like" gynecological disease with distant metastasis, and studies have shown that EMS can carry out distant metastasis through vascular vessels, but the driving factor and its mechanism is not clear. Methods We use EMS animal model and gene knockout technique to explore the role of EMS-induced angiogenesis in EMS metastasis in vivo and in vitro, and clarify the role and molecular mechanism of oxLDL in promoting EMS induced angiogenesis. Results We found that microvascular density (MVD) in metastasized ectopic endometrium and eutopic endometrial tissue were higher than the normal endometrial tissue, and the plasma oxLDL was positively correlated with the distant metastasis of EMS. Furthermore, we clarify that oxLDL enhanced the MVD of endometrial tissue by up-regulating the VEGF-A expression and secretion in endometrial cells. At last, we illustrated the mechanism of oxLDL promoting the VEGF-A expression through the AKT-HIF-1α signaling pathway. Conclusion oxLDL is a risk factor promoting the EMS distant metastasis by up-regulating VEGF-A expression and secretion through AKT-HIF-1α signaling. This founding may provide theoretical support and therapeutic targets for the clinical prevention and treatment of EMS.

show abstract

Downregulation of hsa_circ_0004543 Activates oxLDL-Induced Vascular Endothelial Cell Proliferation and Angiogenesis

Cited by 11 publications

References 28 publications

Oxidized LDLs as Signaling Molecules

Oxidized LDLs as Signaling Molecules

Circular RNA circ_0026218 Suppressed Atherosclerosis Progression via miR‐338‐3p/SIRT6 Axis

oxLDL promotes EMS-induced angiogenesis by up-regulating VEGF-A expression and secretion of endometrial cells

Contact Info

Product

Resources

About